Excessive brain
lactate, as may develop in
cerebral ischemia, has been implicated as a major cause of irreversible cell damage. With an experimental model that produces
cerebral ischemia by bilateral carotid
ligation combined with systemic
hypotension, previous studies have shown that treatment with 25 mg/kg
sodium dichloroacetate (DCA) is effective in reducing brain
lactate more quickly than no treatment at all. Because higher doses of DCA may be more effective, the main objective of our study was to examine the dose-response of brain tissue
lactate to DCA. In addition, other metabolites that may be indirectly affected by this response (eg,
glucose,
glycogen,
ATP, and
phosphocreatine) also were measured. Adult male Wistar rats were assigned to experimental and treatment groups, and real or
sham ischemia was induced as described in our previous article. After 30 minutes of reperfusion, rats were euthanized by in situ freezing of the brain. Cerebral cortex, hippocampus, and cerebellum were analyzed bilaterally. There was no effect of DCA dose on
glucose or
glycogen. When compared with hippocampus,
lactate was higher in the cerebral cortex after
ischemia, and DCA was more effective in reducing those levels. This is evidence of a lower metabolic rate in hippocampus than in cortex. Cerebellum did not exhibit an increase in
lactate; therefore, it can serve as an in situ tissue control for that metabolite. Significantly different levels of metabolites in one hemisphere of some DCA-treated ischemic rats appeared to reflect a dose effect of DCA on
lactate and a significant change in
ATP and
phosphocreatine at the higher doses.(ABSTRACT TRUNCATED AT 250 WORDS)